Synthesis and hybridization properties of l-oligodeoxynucleotide analogues fixed in a low anti glycosyl conformation

We have synthesized l-type enantiomers (cU and cA) of nucleoside analogues, whose glycosyl bonds are fixed in a low anti conformation (ap glycosyl conformation, [small chi][approximate] 180[degree]), and incorporated them into oligonucleotides to evaluate the hybridization ability with natural DNA a...

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Bibliographic Details
Published in:Organic & biomolecular chemistry 2004-01, Vol.2 (2), p.183-189
Main Authors: Urata, Hidehito, Miyagoshi, Hidetaka, Kumashiro, Tetsuya, Yumoto, Takashi, Mori, Keiji, Shoji, Keiko, Gohda, Keigo, Akagi, Masao
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Carbohydrate Conformation
Circular Dichroism
DNA - chemistry
Drug Stability
Glycosides - chemical synthesis
Glycosides - chemistry
Glycosides - metabolism
Models, Molecular
Nucleic Acid Conformation
Nucleic Acid Denaturation
Nucleic Acid Hybridization
Nucleosides - chemistry
Oligonucleotides - chemical synthesis
Oligonucleotides - chemistry
Oligonucleotides - metabolism
Phosphoric Diester Hydrolases - metabolism
RNA - chemistry
Snake Venoms
Sodium Chloride - chemistry
Stereoisomerism
Temperature
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Summary:We have synthesized l-type enantiomers (cU and cA) of nucleoside analogues, whose glycosyl bonds are fixed in a low anti conformation (ap glycosyl conformation, [small chi][approximate] 180[degree]), and incorporated them into oligonucleotides to evaluate the hybridization ability with natural DNA and RNA sequences. Although the incorporation of the modified nucleosides into oligonucleotides decreased the hybridization ability with unmodified complementary DNA sequences, the fully-substituted 12mers (cU(12) and cA(12)) still retained the hybridization ability with the complementary unmodified DNA 12mers, regardless of their unnatural l-chirality. In contrast, cU(12) and cA(12) showed different hybridization behavior with complementary unmodified RNA 12mers. cU(12) forms a more stable duplex with rA(12) than the corresponding natural 12mer (dT(12)), whereas cA(12) cannot hybridize with rU(12). Based on the model structure of cU(12)-rA(12), we discuss these experimental results.
ISSN:1477-0520
1477-0539
DOI:10.1039/b312276j